Systematic Review

Iranian Journal of Otorhinolaryngology, Vol.30(2), Serial No.97, Mar 2018

Tonsillar Lymphoma in Children According to Age Group:

A Systematic Review
Guilherme -Machado de Carvalho1, *Henrique- Furlan Pauna1, Agrício- Nubiato Crespo1,
Reinaldo- Jordão Gusmão1, Alexandre- Caixeta Guimarães1
Abstract
Introduction:
Lymphoma is a common malignant tumor of the head and neck occurring during childhood. Early
diagnosis is very important in terms of prognosis in patients with tonsillar lymphoma.Our objective
was to evaluate the clinical manifestations of pediatric tonsillar lymphoma according to different age
groups.

Materials and Methods:

A systematic review of available English, Spanish, or Portuguese literature from January 1996 to June
2012 was performedin the BIREME, Cochrane, IBECS, Lilacs, PubMed/Medline, SCIELO, and
Scopus databases, using “tonsillar lymphoma” and “children” as keywords. Inclusion criteria were
pediatric case reports, patients aged up to 18 years, and information on clinical features at the time of
diagnosis.

Results:
Out of 87 identified publications, 13 articles were selected describing 53 patients. Tonsillar
asymmetry was the most common sign. Snoring is a common sign in patients aged under 5 years;
clinical lymphadenopathy is frequent among patients aged between 6 and 10 years; and dysphagia is a
common sign in patients between 11 and 18 years of age. Burkitt’s lymphoma is the most common
form among all ages studied, followed by B-cell lymphoma.

Conclusion:
Clinical manifestations differ according to age group. However, tonsillar asymmetry is the most
frequent sign regardless of age group.

Keywords:
Children, Lymphoma, Tonsillar neoplasm, Lymphadenopathy, Tonsillar asymmetry.

Received date: 28 Aug 2017

Accepted date: 29 Jan 2018

1
Department of Otorhinolaryngology, Head and Neck Surgery, University of Campinas, Campinas, São Paulo,
Brazil.
*
Corresponding Author:
Department of Otorhinolaryngology, Head and Neck Surgery, University of Campinas (UNICAMP), 251 Vital
Brasil Street, Campinas-SP, 13083-888, Brazil.
Tel: +55 19 996012243, E-mail: h_pauna@hotmail.com

69

Introduction
Lymphoma is a frequent malignant tumor of
the head among pediatric patients, and chronic
lymphadenopathy of the neck is one of the
main clinical signs. Among the types of
lymphoma, non-Hodgkin lymphoma has the
highest incidence in this pediatric population
(1–4). Up to 20% of patients have extra-nodal
involvement, with the most frequent site being
the palatine tonsil (3,5,6). Some studies have
noted the involvement of Waldeyer’s ring in
15% of pediatric cases of lymphoma (5,7,8).
According to the Ann Arbor Staging System
(9), the initial stage and the size of the tonsillar
lymphoma at diagnosis are related to survival
rate free of disease (4,5,9,10).
Asymmetry of the palatine tonsils also seems
to be related to tonsillar lymphoma. Recently,
a meta-analysis and systematic review showed
an association between asymmetry of the
palatine tonsils and tonsillar lymphoma (8,10).
These studies also demonstrated that tonsillar
asymmetry, changes in the appearance of the
tonsil, and lymphadenopathy are common in
the pediatric population with tonsillar
lymphoma (8,10).
Early diagnosis and treatment are both
important in terms of the prognosis of tonsillar
lymphoma. Therefore, knowledge of the most
frequent clinical features of pediatric
lymphoma according to each age group is a
useful tool for identifying patients with
suspected tonsillar lymphoma (1,5,10).
Although children can present different
clinical manifestations of the disease with age,
no previous studies or systematic reviews have
compared clinical manifestations of tonsillar
lymphoma in children according to age
groups. Therefore, this study aims to describe
the main clinical manifestations of tonsillar
lymphoma and correlate with each age group
by means of a systematic review.
Materials and Methods
This systematic review of the literature
searched for studies on BIREME, Cochrane,
IBECS, Lilacs, PubMed/Medline, SCIELO, and
Scopus. The studies were in English, Portuguese,
or Spanish and reported on lymphoma of the
tonsils in children. No regional limitations were
applied and children from different countries
were included. The studies for this review were
dated between January 1996 and June 2012. The
70 Iranian Journal of Otorhinolaryngology, Vol.30(2), Serial No.97, Mar 2018
Carvalho GM, et al
year 1996 was randomly selected to simplify the
search and because there were just a few articles
before that year, and many of them were not
available in the internet. Duplicates were
excluded manually. The MeSH terms and
keywords used for this systematic review were
“tonsillar lymphoma” and “children”. Two of the
authors (GMC and ACG) were responsible for
searching and reading all the selected studies.
Importantly, this systematic review followed the
Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (PRISMA) criteria
and the recommendations of the Cochrane
Collaboration (11).
The inclusion of studies was analyzed by both
of the authors. Original reports and case reports
were permitted, and included patients aged up
to 18 years and a clinical description of the
palatine tonsils at the time of the diagnosis. In
addition, all included studies had a
histopathological analysis confirming a
diagnosis of lymphoma. However, since
tonsillar lymphoma is a rare condition in the
pediatric age group, all case reports were
included to increase the sample size and to
avoid any potentially important loss of
information. Review articles with no
description of clinical cases and those with no
clear definition for the presence or absence of
lymphoma of the palatine tonsils were
excluded. Thereby, studies with no correlation
of age and clinical features were also excluded.
Any clinical features not mentioned in the
studies were considered absent during the
evaluation of the authors.
We performed a preliminary selection of
relevant articles by reading the title and
abstracts, and excluded studies as per our
inclusion criteria; the remaining papers were
then fully read. Both authors independently
read the articles and extracted relevant data
regarding the review; discrepancies were
resolved by mutual consensus.
Definition of the age groups
Patients were divided into three groups
according to age. Group I included patients up
to 5 years of age, Group II included patients
aged between 6 and 10 years, and Group III
included patients between 11 and 18 years of
age. The division into three age groups was
performed by the authors when collecting the
available data. Therefore, we could observe and
Lymphoma in Children

correlate clinical features according each age We found 87 published articles using the MeSH
group, searching for a specific or satellite sign terms; however only 13 (15%) were included in
that could suggest lymphoma in each of the this systematic review that matched to our
groups. criteria. Overall, we obtained the clinical data
for 53 tonsillar lymphoma patients, and
Statistical analysis analyzed their clinical features (Table.1).
Clinical features among the three groups were
compared using the -square test, with p-values Table 1: Summary of the age groups and
smaller than 0.05 considered statistically characteristics of patients included in this systematic
review.
significant. The statistical analysis was
performed using the software Sigma XL Author Age (years) Age group Sex
Sayed K et al 17 III F
version 6.22 (SigmaXL® Inc, Canada). Sayed K et al 16 III F
Sayed K et al 16 III M
Ethics Sayed K et al 15 III F
This study was approved by our Institution’s Banthia et al 14 III M
Sayed K et al 14 III M
Ethical Committee. Dolev Y et al 13 III F
Sayed K et al 13 III M
Results Sayed K et al 13 III M
Dolev Y et al 12 III M
In total, 147articles were found relating to Sayed K et al 12 III F
lymphoma of the tonsils in children, from Sayed K et al 12 III M
Tewfik TL 12 III M
which, 60 duplicates were excluded. Of the 87 Dolev Y et al 10 II M
remaining studies, 42 were excluded because of Garcia Ortega 10 II M
a lack of clinical data (many focused on Gheoghe et al 10 II M
Tewfik TL 10 II M
pathology, immunology, or gene expression). In Dolev Y et al 9 II M
addition, two articles were excluded because Sayed K et al 9 II M
they were literature reviews, with no Sayed K et al 9 II F
Tewfik TL 9 II M
description of clinical cases. Two further Garavello et al 8 II F
studies were excluded since they were reports Sayed K et al 8 II M
of cerebellar tonsils diseases. Of the 45 articles Sayed K et al 8 II M
Sayed K et al 8 II M
read in full, five were excluded because they Dolev Y et al 7 II M
provided no detailed information regarding Maitra A et al 7 II M
their case reports; six were excluded because Sayed K et al 7 II M
Sayed K et al 7 II M
the age of the subjects was not reported; 17 Sayed K et al 7 II M
were not case reports of lymphoma of the Sayed K et al 7 II M
Garavello et al 6 II M
tonsils or asymmetric palatine tonsils; three
Papouliakos et al 6 II M
studies were excluded for being reviews of the Smitheringale 6 II M
literature without case reports; and one editorial Smitheringale 6 II M
Carvalho et al 5 I F
was excluded. Ultimately, 13 articles remained Zeglaiou I et al 5 I F
for systematic review (Fig. 1). Sayed K et al 5 I M
Sayed K et al 5 I M
Sayed K et al 5 I ?
Dolev Y et al 4 I F
Sayed K et al 4 I M
Sayed K et al 4 I F
Sayed K et al 3 I M
Sayed K et al 3 I F
Sayed K et al 3 I M
Sayed K et al 3 I M
Sayed K et al 2 I F
Sayed K et al 2 I M
Smitheringale 2 I M
Smitheringale 2 I M
Williams et al 2 I M
Smitheringale 1 I F

Fig 1: Flowchart of the results in the search of F = female, M = male, I = 0 to 5 years; II = 6 to 10 years; III =
lymphoma of the tonsils in children. 11 to 18 years

Iranian Journal of Otorhinolaryngology, Vol.30(2), Serial No.97, Mar 2018 77

 Carvalho GM, et al

Eighteen patients were included in Group I frequent manifestations in Group I. Dysphagia

(patients up to the age of 5 years), 55.0% of (16.7%), fever (11.1%), loss of weight (5.5%),
whom were male. Tonsillar asymmetry and lymphadenopathy (5.5%) were uncommon
(72.2%) and snoring (33.3%) were the most features in this group (Table 2).

Table 2: Description of the clinical features (%) and p-values with -square analysis.
Group I Group II Group III P
(n=18) (n=22) (n=13)
Sex
Male 55.0 90.9 61.5 0.0453+
Female 45.0 9.1 38.5
Lymphadenopathy 5.5 45.5 0.0 <0.001+
Tonsillar asymmetry 72.2 68.2 73.5 0.5595
Palatine tonsils mucosa changes 27.8 22.7 15.4 0.7182
Dysphagia 16.7 13.6 46.2 0.0643
Snoring 33.3 13.6 15.4 0.2675
Fever 11.1 4.5 0.0 0.4
Weight loss 5.5 9.1 0.0 0.5312
+
= statistically significant

Burkitt’s lymphoma was the most common followed by B-cell lymphoma (38.9%) and
type of lymphoma in this age group (55.6%), T/NK lymphoma (5.6%) (Table.3).

Table 3: Description of diagnosed tonsillar lymphoma and its correlation with age and sex.
Lymphoma Patients Mean age Age group Male Female
(n) (range) I II III
(n=18) (n=22) (n=13)
Burkitt’s 31 8.22 (1–17) 10 12 9 23 8
B-cell 15 6.93 (2–15) 7 5 3 10 4
NHL histiocytic 2 10.0 (7–13) – 1 1 1 1
T lymphoblastic 2 6 – 2 – 2 –
Hodgkin 1 10 – 1 – 1 –
T/NK cell 1 5 1 – – – 1
Precursor B-cell
1 7 – 1 – 1 –
lymphoblastic

In Group II (patients aged 6 to 10 years), 22
patients were included. Surprisingly, male
patients were the clear majority of this group,
representing 91% of all cases. Tonsillar
asymmetry was found in 68.2% of cases, and
clinical lymphadenopathy in 45.5% of cases.
Snoring and dysphagia were both described in
13.6% of cases, while weight loss (9.1%) and
fever (4.5%) were also identified in this group.
Burkitt’s lymphoma was diagnosed in 54.5%
of patients, with other types of lymphoma
including B-cell lymphoma (22.7%),
lymphoblastic lymphoma (9.1%), Hodgkin’s
lymphoma (4.5%), histiocytic lymphoma
(4.5%), and precursor B-cell lymphoblastic
lymphoma (4.5%).
InGroup III (patients aged 11 to 18 years),
the majority (61.5%) of the 13 patients were
male. Tonsillar asymmetry was present in
73.5% of cases (becoming the most important
suspicious factor for this age group), and
lymphadenopathy during physical examination
was not present in any case. Dysphagia was
identified in 46.2% of cases. Symptoms such
as weight loss, or fever were not observed in
this group. Burkitt’s lymphoma was again the
most frequently diagnosed lymphoma, in
69.2% of cases, followed by B-cell lymphoma
(23.1%), and one (7.7%) case of histiocytic
lymphoma. Changes in the mucosa covering
the palatine tonsils (i.e. any disturbance in the
appearance of the tonsils) were consistently
present in all three groups; however, this was
more prevalent in Group I than in the other
two groups (27.8%, 22.7%, 15.4% for Group I,
Group II, and Group III, respectively). Finally,
immunosuppression and radiotherapy had no
relevant difference among the three groups.

72 Iranian Journal of Otorhinolaryngology, Vol.30(2), Serial No.97, Mar 2018

Lymphoma in Children
Statistical analysis showed significant
differences results for gender distribution
(P=0.045) and for lymphadenopathy (P=0.009)
between the groups.
Discussion
Tonsillectomy is the most common surgical
procedure performed by an otolaryngologist
(12). Enlargement of the palatine tonsils
according to Brodsky’s criteria, recurrent
infections according to Paradise’s criteria,
sleep obstructive apnea, and asymmetrical
enlargement of the palatine tonsils (suspicious
of malignancy) are common indicators for the
procedure (12). Because non-Hodgkin’s
lymphoma is the most common malignant
disease within the lymphatic Waldeyer’s ring
(occurring up to 80% of the time in the
palatine tonsils), an otolaryngologist should
suspect malignancy in cases of asymmetry of
the palatine tonsils associated with other signs
and symptoms (3).
Guimarães et al. found that asymmetric tonsils
were present in 73.2% cases of lymphoma.
They also found a relationshipbetween the
asymmetry of the tonsils and lymphoma
(a likelihood ratio of 43.5 for children with
asymmetric tonsils, and a likelihood ratio of
8938.4 for children with asymmetric tonsils
and other suspicious signs of malignancy)
(10). In another study, Guimarães et al.
observed tonsillar enlargement in 72.7% of
children, cervical lymphadenopathy in 30.3%,
and the presence of B symptoms in 16% of
patients (8). Unlike this study, the present
article describes clinical features separately
according to different age groups. We found
that the majority of cases of male patients
were within the group of children aged from 6
to 10 years; also, we found that
lymphadenopathy was the most frequent
finding within this group, with statistically
significant difference between groups
(P<0.0001).
Asymmetrical enlargement of the palatine
tonsils is considered a dilemma for many
otolaryngologists due to the risks of the
tonsillectomy itself, such as post-operative
bleeding and pain, and also the risk of general
anesthesia (13). A systematic review
performed by Hwang et al. showed no
evidence that would justify tonsillectomy in
cases of tonsillar asymmetry without any other
Iranian Journal of Otorhinolaryngology, Vol.30(2), Serial No.97, Mar 2018 77
associated symptoms in both children and
adults. However, this study suggested that the
surgical team perform the surgery in cases of
widespread lymphadenopathy with rapid
increase, or when systemic symptoms are
associated (14).
Tumors of the head and neck, especially in
pediatric patients, may present in many ways,
and generally as a growing painful mass in the
neck, or as systemic symptoms such as fever
or weight loss. According to the variability
and location of the tumor, symptoms such as
dysphagia, hoarseness, stridor, involvement of
cranial nerves, epistaxis, facial asymmetry, or
tearing might occur (2).
Geographical differences should also be
highlighted (2). According to the International
Classification of Childhood Cancer,
approximately 77,111 cases of pediatric cancer
in children up to 14 years of age were
registered between 1978 and 1997 in Europe
only. Among these cases, only 0.9% were
diagnosed with lymphoma (1). In the United
Kingdom, a double peak of incidence of
Hodgkin’s lymphoma and B-cell
lymphomawas observed; the first is common
in patientsaged 20 to 39 years and the second
is more common in patients aged 70 to 79
years (15). Hodgkin’s lymphoma was reported
in 4% of children aged up to 14 years, and in
12% of patients aged 15 to 30 years in the
United States (9). In Equatorial Africa,
approximately 50% of patients with pediatric
neoplasms are diagnosed with lymphoma (9).
Our study shows that tonsillar asymmetry is
the most common finding across the three age
groups, making it an important factor during
medical evaluation. However, the distribution
of tonsillar asymmetry between the three
different age groups is quite similar and must
be considered a suspicious sign among all age
groups. On the other hand, many studies have
found no malignancy in the palatine tonsils
after tonsillectomy. For example, Oluwasanmi
et al. (2008) presented two patients among 87
that were diagnosed with lymphoma, and
Randall et al. (2007) found an incidence of
0.011% of malignancy among 54,901 adult
patients with tonsillar asymmetry (14). In
1996, Dohar and Bonillareviewed 2012
tonsillectomies in children due to tonsillar
asymmetry, and found only one (0.049%) case
of lymphoma. According to Berkowitz and

Mahadevan, no cases of lymphoma were
foundafter reviewing the charts of 46 pediatric
patients with exclusive signs of tonsillar
asymmetryin 1999 (12).
According to Papouliakos et al., tonsillar
asymmetry must be considered a “high risk”
for malignancy in adults with a previous
history of neoplasm, firm nodule of the neck,
visible lesions within the palatine tonsil,
lymphadenopathy, and systemic symptoms.
Additionally, Vasilakaki et al. showed a peak
of incidence between the sixth and seventh
decades, and a slight predominance among
male patients. For the pediatric group, the
presence of unilateral enlargement of the
palatine tonsils, lymphadenopathy of the neck,
or systemic symptoms would already be
indicative of malignancy (16–18).
Our study reinforces the suspicion of
malignancy in cases of asymmetrical
enlargement of the palatine tonsils in children,
especially when accompanied by other signs
and symptoms such as fever, dysphagia,
snoring, or cervical lymphadenopathy. A final
recommendation for tonsillectomy in this
group of patients seems a viable option since
therapeutic possibilities and survival rates
increase when early diagnosis is performed.
Conclusion
We observed that tonsillar asymmetry was
the most prevalent symptom of lymphoma in
children. Lymphadenopathy is usual in
patients aged from 6 to 10 years. Signs such as
fever and weight loss had no significant
relationship with any group evaluated.
In patients aged up to 5 years, we can
consider tonsillar asymmetry and snoring as
the most common clinical manifestations,
while between the ages of 6 and 10 years,
tonsillar asymmetry and lymphadenopathy are
more common. Finally, between 11 and 18
years of age, tonsillar asymmetry and
dysphagia are the most frequent findings.
Burkitt's lymphoma is more common in all
groups, followed by B-cell lymphoma.
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